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Review
. 2021 Oct 14;13(10):2065.
doi: 10.3390/v13102065.

Toll-like Receptors in Viral Encephalitis

Olivia Luise Gern  1   2 , Felix Mulenge  1 , Andreas Pavlou  1   3   4 , Luca Ghita  1   5 , Imke Steffen  6 , Martin Stangel  7 , Ulrich Kalinke  1   8
Affiliations
Review

Toll-like Receptors in Viral Encephalitis

Olivia Luise Gern et al. Viruses. .

Abstract

Viral encephalitis is a rare but serious syndrome. In addition to DNA-encoded herpes viruses, such as herpes simplex virus and varicella zoster virus, RNA-encoded viruses from the families of Flaviviridae, Rhabdoviridae and Paramyxoviridae are important neurotropic viruses. Whereas in the periphery, the role of Toll-like receptors (TLR) during immune stimulation is well understood, TLR functions within the CNS are less clear. On one hand, TLRs can affect the physiology of neurons during neuronal progenitor cell differentiation and neurite outgrowth, whereas under conditions of infection, the complex interplay between TLR stimulated neurons, astrocytes and microglia is just on the verge of being understood. In this review, we summarize the current knowledge about which TLRs are expressed by cell subsets of the CNS. Furthermore, we specifically highlight functional implications of TLR stimulation in neurons, astrocytes and microglia. After briefly illuminating some examples of viral evasion strategies from TLR signaling, we report on the current knowledge of primary immunodeficiencies in TLR signaling and their consequences for viral encephalitis. Finally, we provide an outlook with examples of TLR agonist mediated intervention strategies and potentiation of vaccine responses against neurotropic virus infections.

Keywords: CNS; Toll-like receptors; astrocytes; microglia; neurons; viral encephalitis; viruses.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
TLR expression in neurons from mice and humans. Virtually all TLRs known in the murine and human system are expressed in neurons. However, the expression of TLR5 in neurons from mice and TLR9 and TLR10 in neurons from humans are controversially discussed [70,111,113,114,118,122,123,125,126,127,128,129,130,137].
Figure 2
Figure 2
TLR expression in astrocytes. Most TLRs known are expressed in human and murine astrocytes, except for TLR8 in both systems, and TLR7, TLR11 and TLR12 in mice [70,108,111,112,115,120,121,125,126,137].
Figure 3
Figure 3
TLR expression in microglia. Human and murine microglia express a high number of TLRs, whereas TLR11 and TLR12 were not detected in the murine system and the expression of TLR10 remains to be defined [70,108,111,115,121,122,125,126,131,137].
See this image and copyright information in PMC

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